Hippocampal connexin 43 expression in human complex partial seizure disorder

Hippocampal connexin 43 expression in human complex partial seizure disorder
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DOI:
10.1006/exnr.1997.6467
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发表时间:
1997-05-01
影响因子:
5.3
通讯作者:
Edvardsen, K
Edvardsen, K
中科院分区:
医学2区
文献类型:
--
作者:
Elisevich, K;Rempel, SA;Edvardsen, K

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间隙连接蛋白的细胞产生的增加和癫痫病灶的神经胶质合胞体中间隙连接数量的增加已被提出作为放电同步的可能机制。为了研究这个问题,对间隙连接蛋白连接蛋白 43 mRNA 和蛋白质丰度进行了 Northern 和 Western 印迹分析,对从患有复杂部分性癫痫症的患者身上切除的海马组织进行了分析,这些患者来自内侧颞区,特别是海马体。将来自 15 名患有医学上难治性癫痫发作的患者的样本与来自 5 名需要治疗的非癫痫患者的样本进行了比较。在危及生命的情况下进行颞叶切除术。 15 名癫痫患者中的 6 名接受了无创电图记录,而其余 9 名患者需要脑内电极进行术外记录,因此显示出比无创记录更离散的焦点。在癫痫患者组中,主要在星形胶质细胞中表达的连接蛋白 43 mRNA 平均水平下降,特别是对于那些需要颅内电极放置的病例,其中发作更明确地确定为海马内。致癫痫和非致癫痫海马组织中连接蛋白 43 蛋白的定量显示表达没有显着差异。尽管 mRNA 平均值显示下降,但术后临床结果显示与我们癫痫人群中的 mRNA 或蛋白质表达均无相关性。研究结果表明,实际上并没有 mRNA 上调,也没有因致癫痫性的发展而导致连接蛋白 43 蛋白的产生增加。相反,间隙连接作为同步或电传播的同盟机制中致癫痫性底物的影响可能是膜结合间隙连接的动态状态(开放与闭合)的函数。 (C) 1997 年学术出版社。
An increase in the cellular product-ion of gap junction proteins and increased numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have been proposed as a possible mechanism underlying synchronization of discharge. To study this issue, both Northern and Western blot analyses of the gap junction protein connexin 43 mRNA and protein abundance were performed on hippocampal tissue resected from patients presenting with a complex partial seizure disorder arising from the medial temporal area and the hippocampus ill particular, Samples from 15 patients with medically intractable seizures were compared to those from 5 nonepileptic patients requiring; temporal lobectomy in Life-threatening situations. Six of the 15 epileptic patients underwent noninvasive electrographic recording, whereas the remaining 9 patients required intracerebral electrodes for extraoperative recording and therefore showed a more discrete focality than the noninvasive recordings. A decline in the mean levels of connexin 43 mRNA expressed predominantly in astrocytes was noted in the epileptic patient groups, particularly for those cases requiring intracranial electrode placement where ic tal onset was more clearly established to be intrahippocampal., Quantitation of connexin 43 protein in both epileptogenic and nonepileptogenic hippocampal tissues showed no significant differences in expression. Although mean values for mRNA showed a decline, clinical outcomes postoperatively showed no correlation with either mRNA or protein expression individually in our epileptic population The findings indicate that there is effectively no upregulation of mRNA and no increased production of connexin 43 protein in response to the development of epileptogenicity. Rather it appears the influence of gap junctions as a substrate of epileptogenicity in ally mechanism(s) underlying synchrony or electrical propagation may be a function of the dynamic state (open versus closed) of the membrane-bound gapjunction. (C) 1997 Academic Press.